Laminin is a trimeric protein composed of three strands including an α (alpha) chain, a β (beta) chain, and a γ (gamma) chain. Based on combination of five types of α (alpha) chain, three types of β (beta) chain, and three types of γ (gamma) chain, at least fifteen isomers are known to be present. Among them, laminin-332 (α3β3γ2 (alpha 3 beta 3 gamma 2), i.e., laminin-5 according to previous nomenclature) is found in great amount in the basal membrane which is present between epidermis and dermis, and it is believed to play an important role for maintaining structure and function of the skin (Non-Patent Document 1). Laminin-332 knockout mice demonstrated separation of the epidermis from the dermis to form vesicles, exhibiting the phenotype which is identical to junctional epidermolysis bullosa, i.e., a human hereditary disorder, and as a result laminin-332 was proven to be essential for adhesion of epidermis on the dermis (Non-Patent Document 2). Further, when a purified sample of laminin-332 is added to a skin equivalent model in which keratinocytes are cultured on a collagen gel embedded with human fibroblasts, the basal membrane formation is enhanced (Non-Patent Document 3). Plasmin is a protease for activated proteins produced by epidermal cells and it cleaves off laminin-332 α (alpha) 3 subunit amino terminal peptide and the carboxy terminal peptide, and β (beta) 3 subunit amino terminal peptide. Each of the cleaved fragments includes a recognition site for substrate adhesion molecule in the cell and a binding site for type VII collagen. Thus, the laminin-332 obtained by digestion with plasmin reduces adhesion ability for keratinocytes. Further, the laminin-332 obtained by digestion with plasmin lowers affinity for type VII collagen. For such reasons, it is believed that skin aging caused by UV irradiation or others are involved in the digestion of laminin-332 by plasmin and impaired function of a basal membrane caused thereby (Non-Patent Document 4).
Thus, by stimulating laminin-332 production, there is a possibility of suppressing and/or improving the skin aging caused by UV irradiation or others. With respect to the factors which stimulate laminin-332 production, it has been recently reported that HIF1 (Non-Patent Document 5) and Smad4 (Non-Patent Document 6) induce transcription of α (alpha) 3 subunit gene. However, HIF1 is a transcription regulator which responds to an environmental stimulation like lack of oxygen and mechanical stimulation, and it is also up-regulated by a proinflammatory cytokine. Smad4 is a transcription regulator involved with signal transduction of TGF-β (beta). All of these regulators are proteins with high molecular weight and their activities are controlled by modification like phosphorylation or state of association with other subunits. For such reasons, it is impossible that they are used for stimulating laminin-332 production according to direct administration to a living body to deliver them to epidermal cells in a skin tissue. Further, as they are all regulated by a broad range of regulating factors and have a significant influence on function of a living body like inflammatory response in addition to stimulating laminin-332 production, it is hardly used routinely with safety.